Saccharomyces cerevisiae (yeast) has been genetically modified to express CEA protein and employed as a heat-killed immune-stimulating, therapeutic cancer vaccine (GI-6207). A previous phase I study with GI-6207 demonstrated safety, bio-marker stabilization and enhanced immune response in some patients. CEA is over-expressed in multiple malignancies, including medullary thyroid cancer (MTC). The recently FDA-approved therapies for metastatic MTC (vandetanib, cabozantinib) come with significant toxicity and are reserved for symptomatic/progressive disease. There is a large population of asymptomatic MTC patients with small tumor burden and/or disease that remains indolent. The standard management of these patients is observation. Preliminary data suggest that tumor growth rate (as measured by CEA and calcitonin) is a quantifiable variable within a 3-6 month time-frame. Retrospective data from prostate cancer studies suggest that vaccines can alter growth rates within 3-4 months. We hypothesize that GI-6207 can alter tumor growth rate in this asymptomatic, indolent MTC patient population, and potentially impact long term outcome. A phase 2 study at the NCI will evaluate the effect of GI-6207 on calcitonin growth rates in metastatic MTC. 34 patients with minimally symptomatic, radiographically-evaluable, metastatic MTC will be randomized 1:1. Arm A will receive vaccine for a year from the time of enrollment. Arm B will receive the same schedule vaccine after a period of 6 months of surveillance. GI-6207 will be administered subcutaneously at 4 sites at 10 yeast units/site, every 2 weeks for 7 visits (day 1, 15, 29, 43, 57, 71, 85), then monthly up to 1 year of treatment. The primary end point will compare the effect of GI-6207 on calcitonin growth rate kinetics between the vaccine and surveillance arms at 6 months. Secondary end points include immunologic responses (CEA-specific T cells, effector/regulatory T-cell ratio, natural killer cells, myeloid derived suppressor cells) objective responses, time to progression, and changes in CEA kinetics. If this trial can prospectively demonstrate that vaccines can alter tumor growth rate, and such changes are associated with clinical outcomes, then changes in tumor growth rate may become a clinical metric to evaluate vaccine efficacy in MTC and other populations. The study opened in March of 2013 and 8 patients have been enrolled.